Genetic Variant NM_004145.4:c.340G>A (chr19-17102057-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004145.4(MYO9B):c.340G>A(p.Ala114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000881 in 1,612,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

MYO9B
NM_004145.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.419

Publications

1 publications found

Variant links:

Genes affected

MYO9B (HGNC:7609): (myosin IXB) This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYO9B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021104068).

BS2

High AC in GnomAd4 at 44 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9B	NM_004145.4	MANE Select	c.340G>A	p.Ala114Thr	missense	Exon 2 of 40	NP_004136.2
	MYO9B	NM_001130065.2		c.340G>A	p.Ala114Thr	missense	Exon 2 of 40	NP_001123537.1	Q13459-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYO9B	ENST00000682292.1	MANE Select	c.340G>A	p.Ala114Thr	missense	Exon 2 of 40	ENSP00000507803.1	Q13459-1
MYO9B	ENST00000595618.5	TSL:1	c.340G>A	p.Ala114Thr	missense	Exon 2 of 40	ENSP00000471457.1	Q13459-2
MYO9B	ENST00000594824.5	TSL:5	c.340G>A	p.Ala114Thr	missense	Exon 2 of 40	ENSP00000471367.1	M0R0P8

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000178

AC:

AN:

247118

AF XY:

0.000149

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.000899

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000888

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000671

AC:

AN:

1460080

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726454

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000850

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51832

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1111848

Other (OTH)

AF:

0.000265

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000289

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41460

American (AMR)

AF:

0.00203

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000359

Hom.:

Bravo

AF:

0.000280

ExAC

AF:

0.0000744

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.1

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.013

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.51

PhyloP100

0.42

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.48

REVEL

Benign

0.087

Sift

Benign

0.64

Sift4G

Benign

0.42

Vest4

0.080

MutPred

0.38

Loss of sheet (P = 0.0457)

MVP

0.51

MPC

0.72

ClinPred

0.014

GERP RS

-3.1

PromoterAI

-0.035

Neutral

(source)

gMVP

0.55

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over